The boundaries of a target product quality profile of certain failure modes can be exploited to construct the operation window, a process design space (PDS), for the granulation process. The purpose of this study is to implement process design and development for the pulsed spray fluid bed granulation (PSFBG) on a laboratory-scale granulator. This work consists of three parts: (1) implementation of Process Analytical Technology (PAT) combined with multivariate data analysis to monitor the formulation characteristics including moisture content, particle size and granule yield; (2) adoption of a new design of experiments (DoE) method Definitive Screening Design (DSD), with the well-established PAT monitoring tools, to investigate the process response to the intended changes in the critical process parameters (CPPs); and finally, (3) the definition of a PDS for the PSFBG, within which the acceptable performance of the process is guaranteed. The effects of the process parameters (i.e., the inlet air temperature, inlet air relative humidity, binder spray rate, atomization pressure, pulse cycle and pulse width) on granule size were evaluated. Two different failure modes were identified based on the measured target product quality (granule size) profile: risk of bed collapse due to over-wetting and low granulating efficiency. Using the constructed PDS for desired granulation, the expected final granule attributes can be obtained through properly controlling the process trajectory by adjusting the process parameters. (C) 2018 Elsevier By. All rights reserved.